膜タンパク質ストマチンの三次元構造とその特異的切断プロテアーゼの機能
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概要
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Stomatin is a major integral membrane protein of human erythrocytes, the absence of which is associated with a form of hemolytic anemia known as hereditary stomatocytosis. It is reported that stomatin regulates the gating of acid-sensing ion channels in mammalian neurons. However, the function of stomatin is not fully understood. In the genomic sequence of the hyperthermophilic archaeon Pyrococcus horikoshii, the putative operon-forming genes PH1511 and PH1510 encode stomatin and its partner protein, respectively. The N-terminal region of PH1510p (1510-N) is a serine protease, and specifically cleaves the C-terminal hydrophobic region of stomatin PH1511p. We have determined the first crystal structure of the core domain of stomatin PH1511p (residues 56-234, designated as PhStoCD). This review focuses on the three-dimensional structure of PhStoCD, and discusses the function of stomatin and its specific protease 1510-N. PhStoCD forms a novel homotrimeric structure. Three α/β domains form a triangle of about 50 Å on each side, and three α-helical segments about 60 Å in length extend from the apexes of the triangle. The α/β domain of PhStoCD is partly similar in structure to the band-7 domain of mouse flotillin-2. While the α/β domain is relatively rigid, the α-helical segment shows a conformational flexibility, adapting to the neighboring environment. One α-helical segment forms an anti-parallel coiled-coil with another α-helical segment from a symmetry-related molecule. The α-helical segment shows a heptad repeat pattern, and mainly hydrophobic residues form a coiled-coil interface. The coiled-coil fold observed in the crystal probably contributes to the self-association.